19-17943590-C-G

Position:

• chr19-17943590-C-G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001136203.2(CCDC124):​c.547C>G​(p.Arg183Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000205 in 1,460,632 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000021 (0 hom.)
• Consequence: CCDC124 NM_001136203.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.20

Genes affected

CCDC124 (HGNC:25171): (coiled-coil domain containing 124) Enables RNA binding activity. Predicted to be involved in cell division. Located in cytosol and plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.20460871).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CCDC124	NM_001136203.2	c.547C>G	p.Arg183Gly	missense_variant	5/5	ENST00000445755.7	NP_001129675.1
CCDC124	NM_138442.4	c.547C>G	p.Arg183Gly	missense_variant	5/5		NP_612451.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CCDC124	ENST00000445755.7	c.547C>G	p.Arg183Gly	missense_variant	5/5	2	NM_001136203.2	ENSP00000408730.1
CCDC124	ENST00000597436.5	c.547C>G	p.Arg183Gly	missense_variant	5/5	1		ENSP00000471455.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000205 AC: 3 AN: 1460632 Hom.: 0 Cov.: 34 AF XY: 0.00000413 AC XY: 3 AN XY: 726632

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000270

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

Bravo AF: 0.00000378

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

May 27, 2022

The c.547C>G (p.R183G) alteration is located in exon 5 (coding exon 4) of the CCDC124 gene. This alteration results from a C to G substitution at nucleotide position 547, causing the arginine (R) at amino acid position 183 to be replaced by a glycine (G). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.42
BayesDel_addAF	Benign	-0.072	T
BayesDel_noAF	Benign	-0.34
CADD	Benign	21
DANN	Uncertain	1.0
DEOGEN2	Benign	0.17	T;T
Eigen	Benign	-0.45
Eigen_PC	Benign	-0.44
FATHMM_MKL	Benign	0.38	N
LIST_S2	Uncertain	0.92	.;D
M_CAP	Benign	0.049	D
MetaRNN	Benign	0.20	T;T
MetaSVM	Benign	-0.97	T
MutationAssessor	Uncertain	2.3	M;M
PrimateAI	Uncertain	0.65	T
PROVEAN	Uncertain	-4.2	D;.
REVEL	Benign	0.20
Sift	Benign	0.076	T;.
Sift4G	Benign	0.30	T;T
Polyphen		0.040	B;B
Vest4		0.36
MutPred		0.56		Loss of MoRF binding (P = 0.0399);Loss of MoRF binding (P = 0.0399);
MVP		0.51
MPC		0.50
ClinPred		0.96	D
GERP RS		1.0
Varity_R		0.64
gMVP		0.67

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs1027723934; hg19: chr19-18054399;